The purpose of the proposed research is to expand our understanding of the role of membranes and, in particular, specific membrane lipids during infection of human cells by herpes simplex virus type 1. Our plan is to assess this role through manipulation of virus envelope and host cell membrane composition followed by assay of virus infectivity. Alteration of cell membrane properties will be achieved through use of mutant human cell lines known to harbor genetically-determined membrane defects and through biochemical modification techniques involving incorporation of lipid analogues and specific fatty acids. The results of these studies are expected to shed new light on the determination of host range, tissue preference, and individual susceptibility to virus infection and, possibly, to provide new avenues for the development of drugs effective against enveloped viruses.